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Current studies investigating properties of nanoparticle-reinforced polymers have shown that nanocomposites often exhibit improved properties compared to neat polymers. However, over two decades of research, using both experimental studies and modeling analyses, has not fully elucidated the mechanistic underpinnings behind these enhancements. Moreover, few studies have focused on developing an understanding among two or more polymer properties affected by incorporation of nanomaterials. In our study, we investigated the elastic and thermal properties of poly(acrylamide) hydrogels containing silica nanoparticles. Both nanoparticle concentration and size affected hydrogel properties, with similar trends in enhancements observed for elastic modulus and thermal diffusivity. We also observed significantly lower swellability for hydrogel nanocomposites relative to neat hydrogels, consistent with previous work suggesting that nanoparticles can mediate pseudo crosslinking within polymer networks. Collectively, these results indicate the ability to develop next-generation composite materials with enhanced mechanical and thermal properties by increasing the average crosslinking density using nanoparticles. [ABSTRACT FROM AUTHOR]

Current studies investigating the role of biophysical cues on cell migration focus on the use of culture platforms with static material parameters. However, migrating cells in vivo often encounter spatial variations in extracellular matrix stiffness. To better understand the effects of stiffness gradients on cell migration, we developed a 2.5D cell culture platform where cells are sandwiched between stiff tissue culture plastic and soft alginate hydrogel. Under these conditions, we observed migration of cells from the underlying stiff substrate into the alginate matrix. Observation of migration into alginate in the presence of integrin inhibition as well as qualitative microscopic analyses suggested an adhesion-independent cell migration mode. Observed migration was dependent on alginate matrix stiffness and the RhoA-ROCK-myosin-II pathway; inhibitors specifically targeting ROCK and myosin-II arrested cell migration. Collectively, these results demonstrate the utility of the 2.5D culture platform to advance our understanding of the effects of stiffness gradients and mechanotransductive signaling on adhesion-independent cell migration. [ABSTRACT FROM AUTHOR]

Research over the past few decades has attempted to answer how proteins behave in molecularly confined or crowded environments when compared to dilute buffer solutions. This information is vital to understanding in vivo protein behavior, as the average spacing between macromolecules in the cell cytosol is much smaller than the size of the macromolecules themselves. In our study, we attempt to address this question using three structurally and functionally different model enzymes encapsulated in agarose gels of different porosities. Our studies reveal that under standard buffer conditions, the initial reaction rates of the agarose-encapsulated enzymes are lower than that of the solution phase enzymes. However, the encapsulated enzymes retain a higher percentage of their activity in the presence of denaturants. Moreover, the concentration of agarose used for encapsulation had a significant effect on the enzyme functional stability; enzymes encapsulated in higher percentages of agarose were more stable than the enzymes encapsulated in lower percentages of agarose. Similar results were observed through structural measurements of enzyme denaturation using an 8-anilinonaphthalene-1-sulfonic acid fluorescence assay. Our work demonstrates the utility of hydrogels to study protein behavior in highly confined environments similar to those present in vivo; furthermore, the enhanced stability of gel-encapsulated enzymes may find use in the delivery of therapeutic proteins, as well as the design of novel strategies for biohybrid medical devices. [ABSTRACT FROM AUTHOR]